1. Ischemic Stroke 2010 and the Future
Lawrence R. Wechsler, M.D.
Professor and Chair,
Department of Neurology, University of Pittsburgh
Director, UPMC Stroke Institute

2. Disclosures Consultant: Abbott Vascular, NMT, Ferrer
Steering committee: ACT I, CLOSURE
DSMB: DIAS 3 / 4, SAPPHIRE WW
Scientific Advisory Board and Stockholder: Neurointerventional Therapeutics

3. Outline Medical therapy for stroke prevention Recanalization
Imaging in patient selection
Telestroke

4. Stroke Prevention 2010 Risk factor control BP, diabetes, lipids
Antiplatelet agents
ASA, Plavix, Aggrenox
Anticoagulation
Afib, hypercoagulable states
Carotid revascularization
CEA v. CAS

5. Medical Therapy for Carotid Disease
Study
Year
Surgery (% Stroke /Yr)
Medical Rx (% Stroke/Yr)
Difference
(% Stroke/Yr)
NASCET > 70%
1991
4.5%
13%
8.5%
NASCET 50-69%
1998
3.1%
4.4%
1.3%
ACAS
1995
1.0%
2.2%
1.2%
ACST
2004
2.4%
1.1%

6. Optimal Medical Management 2010
Blood pressure control
< 130 systolic, 85 diastolic
Diuretics, ACE Inhibitors
Lipids
< 70 LDL, > 50 HDL
HbA1c < 7%
Smoking cessation
Lifestyle modification – weight loss, exercise, diet

7. Intensive Medical Therapy for Asymptomatic Stenosis
Kaplan Meier survival free of stroke, death , MI for 468 pts with > 60% asymptomatic stenosis before and after instituting intensive medical therapy
p<0.001
Spence et al. Arch Neurol 2010

8. IV tPA for Acute Stroke
Only FDA approved therapy for treatment of acute stroke
3-4.5 hr window for treatment
Earlier treatment increases chance of good outcome
Limitations – exclusions, large artery disease, reocclusion

9. PROACT II: 90-Day Outcomes Intra-arterial Prourokinase – MCA Occl
(90 days)
r–proUK
(n = 121)
Control
(n = 59)
Absolute ∆ P
————————— % —————————
mRS ≤ 2 40 25 15
0.043
mRS ≤ 1 26 17 9
0.16
Barthel index ≥ 90 41 32
0.24
Barthel index ≥ 60 54 47 7
0.39
NIHSS ≤ 1 18 12 6
0.30
NIHSS > 50% ↓ 50 44
0.46
Mortality 27 -2
0.80
Furlan A, et al. JAMA. 1999;282:

10. PROACT II: MCA Recanalization
Angiogram
P < 0.001
P = 0.003
Furlan A, et al. JAMA. 1999;282:

11. Mechanical Thrombectomy
Concentric Medical
Penumbra
Not yet FDA approved: Ekos, Omnisonics, Lazarus Effect, MindFrame, Phenox

12. MERCI – Recanalization v. Outcome
Smith WS, et al. Stroke. 2005;36:

13. Recanalization v. Infarct Size
RELATIONSHIP BETWEEN RECANALIZATION AND FINAL INFARCT VOLUME IN 159 PATIENTS TREATED WITH IA THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE AT UPMC
P < by ANOVA
Zaidi et al. Stroke 2009

14. Time to Recanalization v. Outcome
Khatri et al Neurology 2009

15. Recanalization by Treatment Modality – UPMC SI
Pts (n)
TIMI 2 – 3
TIMI 3
———————— % ————————
IV/IA t–PA 66 61 25
IA lytic
117 57
Gp IIb/IIIa + lytic 31 81 42
Angioplasty 67 70 40
Intracranial stent 20 90 50
MERCI retriever
204 79
---
DAC 76 88
Penumbra 39 93
I superscripted ®
Grace, remove all lines form tables except:
rule above table
rule below table header
rule below table

16. Recanalization-Outcomes Mismatch
80-90%
RECANALIZATION
40-50%
RECANALIZATION WITH GOOD OUTCOMES
40-50%
RECANALIZATION WITH POOR OUTCOME
Time to Rx
Depth of ischemia
TIMI 2 v. 3
Stroke location
No reflow

17. Tissue vs. Time Window: Selecting the right Patient
< 3 Hrs
> 3 Hrs
Imaging required to assess pathophysiology =
% Patients with Penumbra
Early time is surrogate marker for penumbra
Time From Onset (Hours)
Courtesy MR Rescue Trial

18. DEFUSE: Mismatch associated with good outcomes following reperfusion
Before tPA
NIHSS 16
6 cc
4.5 hrs
After tPA
NIHSS 5
Improved
0 cc
IV tPA
3 cc
65 cc
↓ M2 Flow

19. DEFUSE: IV tPA 3-6 Hrs Favorable Clinical Response*
Target Mismatch with and without Early Reperfusion
Mismatch + ER (n=15) Median NIHSS: 14 Mean Age: 79
67%
19%
Mismatch - ER (n=16) Median NIHSS: 13 Mean Age: 68
Odds Ratio P = 0.011
*NIHSS 0-1 / > 8 pt improvement at 30 days
Albers et al. Ann Neurol 2006

20. PWI / DWI Mismatch - Quantitation

21. Stroke Treatment with IV tPA
Only 2-8% of stroke patients receive IV tPA
> 50% of hospitals < 100 beds
Lack of available stroke specialist in community hospitals major impediment to emergent treatment
Telestroke brings stroke experts to community hospitals

22. Telemedicine for Stroke
Audebert et al. Cerebrovasc Dis 2005

23. Change in tPA Usage Before and After Starting Telestroke – Spoke Hospital
Telestroke increases utilization of IV tPA
Increases percent of patients treated with IV tPA

24. Future of Acute Stroke Therapy
Reduce time to arterial recanalization
Greater TIMI 3 recanalization
Select patients most likely to benefit and less likely to be harmed
Treat patients based on physiology not time
Increase utilization of acute stroke therapy through telemedicine and stroke systems of care